The goal of this project is to evaluate the comparative effectiveness of lipid-lowering and antihypertensive medications among HIV-infected individuals. HIV infection itself may impact metabolic abnormalities such as dyslipidemia leading to cardiovascular disease risk. In addition, the decline in mortality in the developed world for HIV-infected patients resulting from widespread use of highly active antiretroviral therapy has been accompanied by an increase in metabolic complications such as dyslipidemia and hypertension which can result in significant morbidity among HIV-infected individuals including cardiovascular disease, the leading cause of death and morbidity in the US. However, despite the increasing importance of these chronic conditions, uncertainty exists regarding management choices in clinical practice. We plan to use innovative statistical techniques including marginal structural models to account for time dependant confounding and inverse intensity rate ratio-weighted (IIRR) generalized estimating equations to account for the non structured visit schedule to estimate the comparative effectiveness of medications in the treatment of HIV- infected individuals. We will capitalize on the comprehensive clinical data available within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). This study addresses an important question that will impact provider decision-making regarding lipid-lowering and antihypertensive medications and, as a result, improve the clinical care of HIV-infected patients. In addition, this project will advance the methods available for comparative effectiveness analyses in observational settings. Improving these techniques has the potential to improve studies of comparative medication effectiveness studies for other conditions (beyond that of the HIV-infected patients). PUBLIC HEALTH RELEVANCE: The treatment of cardiovascular disease risk factors among HIV-infected patients is complicated by the underlying infection with HIV, the numerous medications that these patients are often prescribed, and often the presence of multiple other comorbidities. Many questions remain unanswered about the effectiveness of medications to treat dyslipidemia and hypertension among these complicated patients. Providers need additional information to base their decisions regarding which of these medications provide optimal treatment strategies among HIV-infected patients particularly as these strategies may differ depending on the antiretroviral medication regimens or other co-morbidities. Careful analysis and interpretation of observational data from very large cohorts with comprehensive clinical data is required to ensure that HIV-infected patients are receiving optimal care to prevent cardiovascular disease.